Despite significant advancements made in the development of anti-retroviral (ARV) therapeutics, infections caused by human immunodeficiency virus (HIV-1) remain a serious threat to human health (Nair et al.; Ruiz et al. 2015). At the early stage of infection, HIV virus penetrates the blood-brain-barrier (BBB) to enter the central nervous system (CNS), causing neuroAIDS as well as the development of latent HIV reservoirs in the CNS (Jayant et al. 2015; Ruiz et al. 2015). Because the natural integrity of the BBB inhibits anti-HIV drugs to penetrate the brain, treatment of neuroAIDS still remains a challenge. Progression of HIV infection can gradually cause neuro-inflammation, neuro-degeneration, and other related diseases such as, for example, HIV-encephalitis (HIVE) (Jayant et al. 2015).
Subsequent to the introduction of combination antiretroviral therapy (ART), HIV-infection-related morbidity and mortality have dramatically decreased; however, currently available antiretroviral agents, such as those involved in highly active antiretroviral therapy (HAART) exhibit certain side effects (e.g., neuro-inflammation), and can inadvertently contribute to the occurrence of neurocognitive impairments such as, for example, memory loss and sleep disturbances (Jayant et al. 2015).
Additionally, neurological disorders associated with HIV-infection can become more severe with patients who consume substances of abuse such as, for example, cocaine (Coc) (Dahal et al. 2015). Coc alters HIV patients' neurobehavior and secretion of neurotransmitters, speeds up cell-to-cell viral infection by as much as 200 times, and facilitates the virus to penetrate the BBB, resulting in the worsening of neuroAIDS disorders. Moreover, Coc is involved in inducing neuronal apoptosis via triggering viral products and potentiates astrocyte toxicity (Dahal et al. 2015). As a result, a better understanding of the progression of HIV infection at cellular level, the potential effects of Coc in HIV patients' brain functions, and the effects of drug resistance upon exposure of Coc in HIV-infected patients is of great diagnostic significance. Such understanding is required to manage and treat disorders such as neuroAIDS in a timely manner.
Considerable efforts have been made to develop novel therapeutic nanoformulations capable of treating CNS disorders caused by HIV infections (Kaushik et al. 2016a; Kaushik et al. 2014a). Currently, enzyme-linked immunosorbent immunoassay (ELISA), real time/quantitative polymerase chain reaction (RT/Q-PCR), and western blot are the most commonly used analytical tools for monitoring HIV infection by estimating p24 antigen, LTR level, and/or protein expression (Shafiee et al. 2015c; Yager et al. 2008). Optical assays-based surface plasmon resonance (SPR) system has also shown utility in quantifying CD4+ cells for detecting the progression of HIV infections (Shafiee et al. 2015c; Yager et al. 2008). Unfortunately, these methods are expensive, time consuming (e.g., a turnaround detection time is on the order of 6-8 hours), and require technical expertise in implementation.
Thus, developing a rapid, sensitive, laboratory-free, point-of-care (POC) analytical tool with reduced form factors (e.g., miniaturized, nanostructure, or paper-based) capable of detecting and monitoring the progression of HIV infections in the CNS remains a critical need.